Iranian Red Crescent Medical Journal. 2013 August; 15(9): 817-22.

DOI: 10.5812/ircmj.7881
Published Online 2013 August 01. Research Article

Carbetocin vs. Syntometrine in Prevention of Postpartum Hemorrhage: a

Double Blind Randomized Control Trial
1 2 3, *
Mansoureh Samimi , Azam Imani-Harsini , Masoumeh Abedzadeh-Kalahroudi
1 Department of Obstetrics and Gynecology, Kashan University of Medical Sciences, Kashan, IR Iran
2 Obstetrician and Gynecologist, Valieasr Hospital, Brojen, IR Iran
3 Trauma Research Center, Kashan University of Medical Sciences, Kashan, IR Iran

*Corresponding author: Masoumeh Abedzadeh-Kalahroudi, Trauma Research Center, Kashan University of Medical Sciences, Kashan, IR Iran. Tel: +98-3615620634, Fax: +98-
3615620634, E-mail: abedzadeh@kaums.ac.ir.

Received: August 23, 2012; Revised: March 16, 2013; Accepted: April 24, 2013

Background: Postpartum hemorrhage is a signicant cause of maternal mortality and morbidity, worldwide.
Objectives: The aim of this study was to compare the efficacy between carbetocin and syntometrine in prevention of postpartum
hemorrhage.
Materials and Methods: This study was a double blind randomized clinical trial that carried out on 200 pregnant women referred
to Shabiehkhani maternity center of Kashan, during 2011. The first group received intramuscular syntometrine and the second group
received intramuscular carbetocin after placental delivery. All of the participants were followed for 24 hours and blood pressure, pulse
rate, uterine tone, hemoglobin concentration at first and 24 hours after delivery, and the need for additional uterotonic drugs and drug
side effects were evaluated. Finally all data were analyzed using t-test, chi square tests and logistic regression.
Results: The mean fall in hemoglobin level in the carbetocin group was significantly lower than the syntometrine group (P < 0.001). Also
there were significant differences between the two groups, regarding additional uterotonic drug requirements (P = 0.002). Moreover
systolic blood pressure and uterine tone immediately and 30 minutes after drug administration were significantly different (P < 0.001).
Incidence rate of tachycardia in the carbetocin group was 13%, in contrast to 5% in the syntometrine group (P = 0.04).
Conclusions: This study revealed that carbetocin is more effective than syntometrine in prevention of postpartum hemorrhages. Thus it
can be used as a good alternative of syntometrine for low-risk women.

Keywords: Carbetocin; Postpartum Hemorrhage; Prevention and Control; Syntometrine

1. Introduction oxytocin and the continuous effect of ergometrine. Pre-

Postpartum hemorrhage (PPH) is a life threatening situ-
ation and one of the important causes of maternal mor-
tality and morbidity, worldwide (1). Annually, 14 million
women suffer from postpartum hemorrhage, of which
about 140,000 individuals die and 1.6 million encoun-
ter anemia and its long term problems (2). Postpartum
hemorrhage is seen in 18% of deliveries (3). Postpartum
hemorrhage prevention is very important. Several stud-
ies have shown that the use of uterotonic agents after pla-
cental separation can reduce the incidence of PPH by up
to 30% - 40% and use of these drugs for PPH prevention is
approved by all researchers (4).
The first uterotonic drug was ergometrine that intro-
duces in 1950, while oxytocin and syntometrine were re-
leased during 1953 and 1963, respectively. Syntometrine is
a combination of 5 IU oxytocin and 0.5 mg ergotamine in
every 1 ml (5, 6). This mixture is one of the most common
uterotonic drugs that is used during the third stage of la-
bour, because this drug has the rapid onset of action of
vious studies have reported that the effects of intramus-
cular (IM) syntometrine are similar with intravenous (IV)
oxytocin (7). Ergotamine may increase blood pressure (5)
and coronary artery spasm (6), as it can cause vasocon-
striction and muscle contraction; therefore in women
with hypertension, asthma or cardiac disease, syntomet-
rine is contraindicated.
On the other hand, carbetocin was introduced during
1987 (8). Carbetocin is a long- acting synthetic analogue of
oxytocin with a half-life of 40 minutes and 80% bioavail-
ability in IM injection. After IM or IV administration of
this drug, uterine contractions start in less than 2 min-
utes (9). Drug dosage is 100 microgram during the third
stage of labour (10).
The common side effects of carbetocin are nausea, vom-
iting, abdominal pain, hypotension, headache, chilling
and pyrexia. Its contraindications are uterine, vaginal or
cervical rupture (8).
Carbetocin makes a longer uterine response compared

Implication for health policy/practice/research/medical education:

This study has implications for midwives and obstetrician for prevention of postpartum hemorrhage.
Copyright 2013, Iranian Red Crescent Medical Journal; Licensee KowsarKowsar Ltd. This is an Open Access article distributed under the terms of the Creative Com-
mons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided
the original work is properly cited.
 Samimi M et al.
with oxytocin in terms of frequency and amplitude of
contractions (11). Moreover, in comparison with oxytocin
or syntometrine, it seems to have fewer gastrointestinal
and cardiovascular side effects (12).
Several studies have compared oxytocin or syntomet-
rine with carbetocin. Most of these studies have shown
that carbetocin is more effective than oxytocin or synto-
metrine in prevention of PPH (13-17). However in other
studies significant differences between these drugs were
not observed (18-20).
Previous studies have reported that the need for ad-
ditional uterotonic drugs in women who received car-
betocin was less than women who received intravenous
oxytocin (12, 19); however in other studies, no significant
differences were observed between the two groups (16, 20).
The need for additional uterotonic drugs represents the
severity of postpartum hemorrhage due to uterine atony,
making it an important variable during the outcome
measurement.
Recent evidence suggests that carbetocin is safe, similar
to oxytocin (13, 14). Moreover, it has fewer adverse effects
compared with syntometrine (16, 18). These data indicate
that carbetocin can be replaced with syntometrine for
the prevention of postpartum hemorrhage.
2. Objectives
Based on our knowledge, there is very limited published
literature, which compares the use of carbetocin and syn-
tometrine in women who delivered vaginally. Therefore
we conducted this randomized trial to compare the effi-
cacy of IM carbetocin with IM syntometrine for the pre-
vention of postpartum hemorrhage.
3. Material and Methods
This study was a double-blind, clinical randomized tri-
al that carried was out on 200 women with a singleton
pregnancy from March 2011 to June 2011 in the delivery
unit of a Shabihkhani Maternity Center in Kashan city
in Iran. Exclusion criteria included chronic hyperten-
sion, preeclampsia, uterine or cervical rupture, asthma,
cardiovascular, renal or liver diseases, grand multiparity,
uterine fibroids, and history of PPH.
Patients were randomized to syntometrine (N = 100) or
carbetocin groups (N = 100). In the syntometrine group,
women received 1 ml of syntometrine (containing 5 units
of oxytocin and 0.2 mg ergometrine) and the carbetocin
group received 1 ml of carbetocin (containing 100 micro-
gram carbetocin) after placental separation. Randomiza-
tion was performed using a random number table. Both
these drugs were coded and packed before recruitment,
and stored at the delivery room. Patients and medical
personnel were blinded to the type of drug.
If oxytocin infusion was in progress, it was discontin-
ued. Maternal blood pressure, pulse rate and uterine to-
818
nicity were checked immediately after administration of
the drugs and repeated 30 and 60 minutes later. Uterine
tonicity was scored from zero to 3 which included atony,
mild, moderate, and severe tonicity respectively.
The primary outcome measure of this study was the as-
sessment of hemoglobin level on admission to the labour
ward and this was compared with hemoglobin level 24
hours after delivery. The secondary outcome measure
was the requirement of additional uterotonic medica-
tion. In our delivery unit, the criteria for additional utero-
tonic usage was estimated blood loss of more than 500
ml with or without hypotension or tachycardia and poor
uterine tonicity. Women were also evaluated for adverse
effects of drugs within 2 hours after delivery.
Eligible women signed the informed consent from and
the study protocol, which was approved by the Clinical Re-
search Ethics Committee of Kashan University of Medical
Sciences. Also this study was registered in the Iranian reg-
istry of clinical trial with this number: 138810212854N2.
3.1. Statistical Analysis
All outcome measures, including the need for addition-
al uterotonic agents, uterine tonicity, blood pressure,
pulse rate, fall in hemoglobin and drugs side effects were
analyzed using Chi-square, Fisher Exact, Student t-tests
and logistic regression. The relative risk (RR) and 95%
confidence intervals (CI) also were calculated. P value of
less than 0.05 (P < 0.05) was considered statistically sig-
nificant.
3.2. Sample Size
Sample size calculations were based on our pilot study,
which showed that mean and standard deviation hemo-
globin level in carbetocin and syntometrine group was
11.35 1.04 g/dl and 11.79 1.06 g/dl. For 5% level of signifi-
cance and 80% power it was necessary to recruit 91 wom-
en for each trial arm. Considering a dropout rate of 10%
the sample size required 100 per group.
4. Results
Figure 1 is a flow chart of the study design. Women in
both groups were comparable in terms of baseline and
birth- related characteristics (Table 1).
The primary and secondary outcome measurements
of each group are shown in Table 2. The mean fall of he-
moglobin concentration after delivery was 0.39 g/dl in
the carbetocin group and 1.04 g/dl in the syntometrine
group, and the difference was significant. The incidence
rate of greater than 10% fall in hemoglobin concentra-
tion was 3% and 35% in the carbetocin and syntomet-
rine group, respectively [RR = 11.6, 95% CI (3.7 - 36.7), (P <
0.001)]. Hemoglobin concentration fall of > 20% was seen
in 3% of women in the syntometrine group but the differ-
ence wasnt significant.
Iran Red Crescent Med J. 2013;15(9)
 Samimi M et al.

Women screened during the study period

(n=500)
147 women did not have inclusion criteria:
Multiple pregnancy
Sever preeclampsia
High risk for PPH

Women eligible for study recruitment

(n=353) 32 Women refused consent
105 women delivered by emergency
cesarean section

Women were randomized

(n=216)

Women received carbetocin Women received

(n=109) syntometrin (n=107)

9 Women refused blood taking 7 Women refused blood taking

after 24 hours of delivery after 24 hours of delivery

Women in Carbetocin Women in Syntometrin

group analyzed (n=100) group analyzed (n=100)

Figure 1. Trial Profile of Recruitment and Randomization to Carbetocin or Syntometrin Groups

Table 1. Baseline and Birth-Related Characteristics of the Study Population

Characteristics Carbetocin (n = 100) Syntometrine (n = 100) P Value
Age (y); Mean (SD) 25.4 (4.1) 24.8 (4.5) 0.35
Gestational age (w); Mean (SD) 38.7 (1.5) 38.8 (1.4) 0.84
Parity; No. (%) 0.65
NulliPara 65 (65) 69 (69)
Multipara 35(35) 31(31)
Induction of labour; No. (%) 75 (75) 76 (76) 0.86
Episiotomy; No. (%) 62 (62) 61 (61) 0.88
Perineal Laceration; No. (%) 5 (5) 11 (11) 0.19
Birth weight (g); Mean (SD) 3208 (152) 3336 (344) 0.45

Eleven percent of women in the syntometrine group
required additional uterotonic agents but 1% of women
in the carbetocin group required the use of additional
uterotonic agents and there were signicant difference
between the two groups [RR = 11, 95% CI (1.44 - 83.6),(P =
0.002)].
The mean uterine tonicity values at different intervals
after drug administration also are shown in Table 2. There
was a difference between the carbetocin group and syn-
tometrine group in terms of uterine tonicity immediate-
ly and 30 minutes after drug injection (P < 0.001).
The mean blood pressure values at different intervals
after drug injection in the two groups are shown in Table
2. There were significant differences between the two
groups in terms of systolic blood pressure immediately,
30 and 60 minutes after drugs injection (P < 0.001) but
not in the diastolic blood pressure at the same times.
None of the women in this study had hypertension
(blood pressure > 140 / 90 mmHg) at 0, 30 and 60 min
after drug injection
Adverse effects of these drugs are presented in Table 3.
Women in the carbetocin group experienced fewer symp-
toms such as nausea, abdominal pain and chill but the
difference wasnt significant.

Iran Red Crescent Med J. 2013;15(9) 819

 Samimi M et al.

Table 2. Primary and Secondary Outcome Measures of the Study Population

Characteristics Carbetocin (n = 100) Syntometrine (n = 100) P-value
Hemoglobin at Onset of Labour (g/dl)a 12.12 1.1 13.02 1.2 0.001
Hemoglobin at 24 Hours after Delivery (g/dl)a 11.71 1.1 11.98 1.3 0.13
Mean Fall in Hemoglobin (g/dl)a 0.41 0.36 1.04 0.78 < 0.001
Percent Fall of Hemoglobin
> 20% 0 (0) 3 (3) 0.08
> 10% 3 (3) 35 (35) < 0.001
Need for Additional Uterotonic 1 (1) 11 (11) 0.002
Uterine Tonicity Immediately after Drug Administrationa 2.11 0.54 1.29 0.47 < 0.001
Uterine Tonicity 30 Minutes after Drug Administrationa 2.01 0.59 1.68 0.46 < 0.001
Uterine Tonicity 60 Minutes after Drug Administrationa 2.04 0.63 1.94 0.23 0.14
Mean Systolic Blood Pressure Immediately after Drug Administrationa 112 91 120 73 < 0.001
Mean Systolic Blood Pressure 30 Minutes after Drug Administrationa 109 78 115 77 < 0.001
Mean Systolic Blood Pressure 60 Minutes after Drug Administrationa 111 69 113 85 0.03
Mean Diastolic Blood Pressure Immediately after Drug Administrationa 71 9 73 8 0.05
Mean Diastolic Blood Pressure 30 Minutes after Drug Administrationa 70 8 71 7 0.57
Mean Diastolic Blood Pressure 60 Minutes after Drug Administrationa 71 7 71 7 0.88
a Data are presented as Mean SD

Table 3. Adverse Effects of Two Drugs in the Study Population

Characteristics Carbetocin (n = 100) Syntometrine (n = 100) P-value
Nausea 2% 3% 0.65
Vomiting 1% 0% 0.5
Chill 0% 1% 0.5
Abdominal Pain 1% 0% 0.5
Hypotension (BP < 90 / 60 mmHg) 0% 2% 0.49
Tachycardia (Pulse 100 Beats per Minute) Immediately After Delivery 13% 5% 0.04

Multivariate analysis with regression logistic showed
that baseline factors such as age parity, gestational age,
induction of labor, episiotomy, perineal laceration, birth
weight and hemoglobin level before delivery was not as-
sociated with fall of hemoglobin level, but the difference
between the two drugs was significant.
5. Discussion
This was the rst randomized controlled trial assess-
ing the effects of carbetocin in Iran. Several randomized
trials have compared oxytocin or syntometrine with car-
betocin. Most of these trials have found carbetocin to be
better than oxytocin or syntometrine in prevention of
PPH (13-17), but in three studies there weren't any signifi-
cant differences between these drugs (18-20).
Our study showed that in the syntometrine group,
mean fall of hemoglobin concentration after delivery
and fall in hemoglobin level more than 10% was higher
than the carbetocin group, and their difference was sig-
nificant. This shows that IM carbetocin is more effective
than syntometrine in prevention of postpartum hemor-
rhage. Several studies have shown that fall in hemoglo-
bin level in the syntometrine group was higher than the
carbetocin group (15-17). These findings are compatible
with our results and indicate the better effect of carbeto-
cin than syntometrin. However Leung and Boucher stud-
ies indicate no difference in the fall of hemoglobin con-
centration between the two groups (17, 18). Our findings
are different from these researches. There may be several
reasons for this, most importantly the difference in the
eligibility criteria (such as type of delivery or high risk of
PPH), type of drug (such as IV oxytocin), syntometrin dos-
age and timing of the intervention.
Our study showed that carbetocin is more effective
than syntometrine in terms of the need for additional
uterotonic agents and the difference was statistically

820 Iran Red Crescent Med J. 2013;15(9)

 Samimi M et al.
signicant. One of the important indicators of post-
partum bleeding is the need for additional uterotonic
agents. Su et al. have shown that the need for additional
uterotonic agents was 13.5% in the carbetocin group and
16.8% in the syntometrine group but the difference wasn't
signicant (20). In addition, the same results have been
shown by several other studies (16, 18, 19).
Our results indicated that there was a difference between
the carbetocin group and syntometrine group in terms
of uterine tonicity after delivery. This issue revealed the
better effect of carbetocin than syntometrin on uterine
tonicity during 24 hours after delivery. Dansereau et al.
have found that carbetocin is more effective than oxytocin
in maintaining uterine tone (14). One study showed that
injection of carbetocin after delivery at a single dose can
cause a uterine contraction in less than 2 minutes and will
continue for two hours (11). However Ngan et al. showed
that uterine tone in the two groups was similar (15).
Based on the findings of this study there was a signifi-
cant difference between the two groups in terms of sys-
tolic blood pressure at 0, 30 and 60 minutes after drug
administration but this difference wasn't significant in
terms of diastolic blood pressure. None of the women
in this study had blood pressures greater than 140/90
mmHg. In one study, significant increases in systolic and
diastolic blood pressure at 30 and 60 min after delivery
were seen in the syntometrine group (16). Although in
the Ngan et al. study, blood pressure was similar between
the two groups (15) and in the Leung et al. research, the
rate of high blood pressure in the carbetocin group was
considerably lower than the syntometrine group (18).
Our findings show that mean and standard deviation
of heart rate between the two groups were statistically
signicant only immediately after drug administration.
Also, the incidence rate of tachycardia (PR > 100BPM) in
the carbetocin group was 13%, in contrast to 5% in the syn-
tometrine group (P = 0.04). A previous study has shown
that carbetocin can cause maternal tachycardia (9, 11). In
the Leung study 21% of women who received carbetocin
had tachycardia, which was significantly greater than
women who received syntometrine (18). This finding is
virtually the same as our results. However in two studies
the pulse rate was similar between the groups (15-17).
In this study the incidence of many adverse effects, such
as nausea, vomiting, chill, abdominal pain and hypoten-
sion was low and similar in the two groups. In the Askar
et al. study, women in the carbetocin group had lower
incidence of nausea and vomiting, and the difference be-
tween the two groups was statistically signicant. Howev-
er, the incidence of other adverse effects such as ushing,
headache, and abdominal pain were low and similar for
both groups (16). Also Leung et al. study has shown that
the incidence of nausea and vomiting in the carbetocin
group is lower than the syntometrine group (18).
The difference between our findings and other studies
in terms of adverse effects and additional uterotonic re-
Iran Red Crescent Med J. 2013;15(9)
quirements could be due to differences in syntometrine
dosage or type of uterotonic drugs that was compared
with carbetocin.
Our results showed that carbetocin is more effective
than syntometrin in prevention of postpartum hemor-
rhage. The need for additional uterotonic agents was
lower in women who received carbetocin; moreover its
adverse effects were low. Therefore it can be concluded
that IM carbetocin is a good alternative of IM syntomet-
rine in low-risk women.
Acknowledgements
We would like to thank all of midwives in shabihkhani
Maternity hospital for their cooperation.
Authors Contribution
Samimi Mansoureh: planning of the project Imani-
Harsini Azam: carrying out of the experimental work;
Abedzadeh- Kalahroudi Masoumeh: analysis of the data
and writing of the paper.
Financial Disclosure
None declared.
Funding/Support
This study was supported in part by grant No 8839 from
Kashan University of Medical Sciences, Kashan, Iran.
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